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Allogeneic hematopoietic cell transplantation is equally effective in secondary acute lymphoblastic leukemia (ALL) compared to de-novo ALL-a report from the EBMT registry
Sadowska-Klasa, A., Zaucha, J. M., Labopin, M., Bourhis, J. H., Blaise, D., Yakoub-Agha, I., Salmenniemi, U., Passweg, J., Fegueux, N., Schroeder, T., et al
Bone marrow transplantation. 2024
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Editor's Choice
Abstract
Secondary acute lymphoblastic leukemia (s-ALL) comprises up to 10% of ALL patients. However, data regarding s-ALL outcomes is limited. To answer what is the role of allogeneic hematopoietic cell transplantation (HCT) in s-ALL, a matched-pair analysis in a 1:2 ratio was conducted to compare outcomes between s-ALL and de novo ALL (dn-ALL) patients reported between 2000-2021 to the European Society for Blood and Marrow Transplantation registry. Among 9720 ALL patients, 351 (3.6%) were s-ALL, of which 80 were in first complete remission (CR1) with a known precedent primary diagnosis 58.8% solid tumor (ST), 41.2% hematological diseases (HD). The estimated 2-year relapse incidence (RI) was 19.1% (95%CI: 11-28.9), leukemia-free survival (LFS) 52.1% (95%CI: 39.6-63.2), non-relapse mortality (NRM) 28.8% (95%CI: 18.4-40), GvHD-free, relapse-free survival (GRFS) 39.4% (95%CI: 27.8-50.7), and overall survival (OS) 60.8% (95%CI: 47.9-71.4), and did not differ between ST and HD patients. In a matched-pair analysis, there was no difference in RI, GRFS, NRM, LFS, or OS between s-ALL and dn-ALL except for a higher incidence of chronic GvHD (51.9% vs. 31.4%) in s-ALL. To conclude, patients with s-ALL who received HCT in CR1 have comparable outcomes to patients with dn-ALL.
PICO Summary
Population
Adults with acute lymphoblastic leukaemia, reported to the EBMT registry (n=9720)
Intervention
A detailed analysis cohort who were transplanted for secondary acute lymphoblastic leukaemia (s-ALL, n=80)
Comparison
Matched controls who were transplanted for de novo ALL (dn-ALL, n=80)
Outcome
The estimated 2-year relapse incidence (RI) was 19.1% (95%CI: 11-28.9), leukemia-free survival (LFS) 52.1% (95%CI: 39.6-63.2), non-relapse mortality (NRM) 28.8% (95%CI: 18.4-40), GvHD-free, relapse-free survival (GRFS) 39.4% (95%CI: 27.8-50.7), and overall survival (OS) 60.8% (95%CI: 47.9-71.4), and did not differ between solid tumour and haematological disease patients. In a matched-pair analysis, there was no difference in RI, GRFS, NRM, LFS, or OS between s-ALL and dn-ALL except for a higher incidence of chronic GvHD (51.9% vs. 31.4%) in s-ALL.
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Fludarabine-treosulfan versus fludarabine-melphalan or busulfan-cyclophosphamide conditioning in older AML or MDS patients - A clinical trial to registry data comparison
Beelen, D. W., Iacobelli, S., Koster, L., Eikema, D. J., van Biezen, A., Stölzel, F., Ciceri, F., Bethge, W., Dreger, P., Wagner-Drouet, E. M., et al
Bone marrow transplantation. 2024
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Editor's Choice
Abstract
A randomized study (acronym: MC-FludT.14/L Trial II) demonstrated that fludarabine plus treosulfan (30 g/m²) was an effective and well tolerated conditioning regimen for allogeneic hematopoietic cell transplantation (allo-HCT) in older patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). To further evaluate this regimen, all 252 study patients aged 50 to 70 years were compared with similar patients, who underwent allo-HCT after fludarabine/melphalan (140 mg/m²) (FluMel) or busulfan (12.8 mg/kg)/cyclophosphamide (120 mg/kg) (BuCy) regimens and whose data was provided by the European Society for Blood and Marrow Transplantation registry. In 1:1 propensity-score matched-paired analysis (PSA) of AML patients, there was no difference in 2-year-relapse-incidence after FluTreo compared with either FluMel (n = 110, p = 0.28) or BuCy (n = 78, p = 0.98). However, 2-year-non-relapse-mortality (NRM) was lower compared with FluMel (p = 0.019) and BuCy (p < 0.001). Consequently, 2-year-overall-survival (OS) after FluTreo was higher compared with FluMel (p = 0.04) and BuCy (p < 0.001). For MDS patients, no endpoint differences between FluTreo and FluMel (n = 30) were evident, whereas 2-year-OS after FluTreo was higher compared with BuCy (n = 25, p = 0.01) due to lower 2-year-NRM. Multivariate sensitivity analysis confirmed all significant results of PSA. Consequently, FluTreo (30 g/m²) seems to retain efficacy compared with FluMel and BuCy, but is better tolerated by older patients.
PICO Summary
Population
Adults aged 50-70 years with primary or secondary AML in complete remission or MDS, receiving a peripheral blood allogeneic transplant (n=1220)
Intervention
Participants in the MC-FludT.14/L trial who received fludarabine-treosulfan conditioning (FluTreo, n=252)
Comparison
Propensity-score matched patients identified from the EBMT registry (n=968) who received fludarabine/melphalan (FluMel, n=338) or busulfan/cyclophosphamide (BuCy, n=630) regimens
Outcome
In 1:1 propensity-score matched-paired analysis (PSA) of AML patients, there was no difference in 2-year-relapse-incidence after FluTreo compared with either FluMel (n=110) or BuCy (n=78). However, 2-year-non-relapse-mortality (NRM) was lower compared with FluMel and BuCy. Consequently, 2-year-overall-survival (OS) after FluTreo was higher compared with FluMel and BuCy. For MDS patients, no endpoint differences between FluTreo and FluMel (n=30) were evident, whereas 2-year-OS after FluTreo was higher compared with BuCy (n=25) due to lower 2-year-NRM. Multivariate sensitivity analysis confirmed all significant results of PSA.
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A nationwide retrospective analysis of allogeneic hematopoietic stem cell transplantation for adult hemophagocytic lymphohistiocytosis
Kim, H., Mizuno, K., Masuda, K., Sakurai, M., Ara, T., Naito, K., Uehara, Y., Yamamoto, G., Osada, M., Machida, S., et al
Transplantation and cellular therapy. 2024
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Editor's Choice
Abstract
[BACKGROUND/OBJECTIVE]: Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening disorder characterized by systemic hyperinflammation. Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only potentially curative treatment for primary and relapsed/refractory HLH, the optimal strategy has not been established. [STUDY DESIGN]: We retrospectively analyzed 56 adult patients (≥ 18 years) with primary and secondary HLH (mainly consisting of Epstein-Barr virus-associated HLH) who underwent allo-HSCT using the registry database of the Japanese Society for Transplantation and Cellular Therapy, including 26 patients who underwent cord blood transplantation (CBT). One-fourth of patients received myeloablative conditioning (MAC), mainly consisting of total body irradiation-based regimens. [RESULTS]: The 3-year overall survival (OS) was 40.6%, while the 3-year cumulative incidences of relapse and non-relapse mortality (NRM) were 19.8% and 39.6%, respectively. In univariable analysis, age at allo-HSCT (the 3-year OS: 27.5% for ≥ 25 years old vs 58.0% for < 25 years old, P = 0.030), conditioning intensity (7.1% for MAC vs 51.8% for reduced-intensity conditioning (RIC), P = 0.003), and donor source (26.0% for CBT vs 52.9% for bone marrow or peripheral blood stem cell transplantation (BMT/PBSCT), P = 0.033) were associated with significantly inferior OS. In multivariable analysis, older age at allo-HSCT (≥ 25 years old) (Hazard ratio [HR], 2.37; 95% CI, 1.01-5.58; P = 0.048), MAC (HR, 2.45; 95% CI, 1.09-5.53; P = 0.031), and CBT (HR, 2.21; 95% CI, 1.04-4.71; P = 0.040) were independently associated with worse OS. In addition, only conditioning intensity predicted higher NRM (the 3-year NRM: 78.6% for MAC vs 26.6% for RIC), while no factors were associated with the relapse rate. [CONCLUSION]: This study includes the largest number of adult HLH patients undergoing CBT. Although the use of CBT is acceptable, BMT/PBSCT are more favorable strategies in allo-HSCT in adult HLH. Regarding conditioning intensity, RIC regimens are more beneficial in this setting.
PICO Summary
Population
Adults with primary or secondary hemophagocytic lymphohistiocytosis (HLH) identified from the Japanese Society for Transplantation and Cellular Therapy registry (n= 56)
Intervention
Allogeneic transplantation: cord blood (n=26), peripheral blood or bone marrow transplant (n=30)
Comparison
None
Outcome
The 3-year overall survival (OS) was 40.6%, while the 3-year cumulative incidences of relapse and non-relapse mortality (NRM) were 19.8% and 39.6%, respectively. In univariable analysis, age at allo-HSCT (the 3-year OS: 27.5% for ≥ 25 years old vs 58.0% for < 25 years old), conditioning intensity (7.1% for MAC vs 51.8% for reduced-intensity conditioning (RIC)), and donor source (26.0% for CBT vs 52.9% for bone marrow or peripheral blood stem cell transplantation (BMT/PBSCT)) were associated with significantly inferior OS. In multivariable analysis, older age at allo-HSCT (≥ 25 years old) (Hazard ratio [HR], 2.37; 95% CI, 1.01-5.58), MAC (HR, 2.45; 95% CI, 1.09-5.53), and CBT (HR, 2.21; 95% CI, 1.04-4.71) were independently associated with worse OS. In addition, only conditioning intensity predicted higher NRM (the 3-year NRM: 78.6% for MAC vs 26.6% for RIC), while no factors were associated with the relapse rate.
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Complex karyotype but not other cytogenetic abnormalities is associated with worse posttransplant survival of patients with nucleophosmin 1-mutated acute myeloid leukemia: A study from the European Society for Blood and Marrow Transplantation Acute Leukemia Working Party
Moukalled, N., Labopin, M., Versluis, J., Socié, G., Blaise, D., Salmenniemi, U., Rambaldi, A., Gedde-Dahl, T., Tholouli, E., Kröger, N., et al
American journal of hematology. 2024
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Editor's Choice
Abstract
In the 2022 European LeukemiaNet classification, patients with nucleophosmin 1 (NPM1)-mutated acute myeloid leukemia (AML) were classified in the adverse-risk category in the presence of high-risk cytogenetics (CG). Nonetheless, the impact of various CG aberrations on posttransplant outcomes remains to be unraveled. This registry study analyzed adult patients with NPM1-mutated de novo AML who underwent their first allogeneic hematopoietic cell transplantation in the first complete remission from 2005 to 2021. A total of 3275 patients were identified, 2782 had normal karyotype, 493 had chromosomal aberrations including 160 with adverse-risk CG, 72 patients had complex karyotype (CK), and 66 monosomal karyotype (MK). Overall, 2377 (73%) patients had FLT3-ITD. On univariate analysis, only FLT3-ITD, minimal/measurable residual disease (MRD) positivity and CK, but not abnormal CG, affected posttransplant outcomes. On multivariable analysis, CK was associated with lower overall survival (OS) (hazard ratio [HR] 1.72, p = .009). In the subgroup of 493 patients with aberrant CG, the 2-year leukemia-free survival (LFS) and OS were around 61% and 68%, respectively. On multivariable analysis for this subgroup, CK and MRD positivity were associated with increased risk of relapse (HR 1.7, p = .025; and 1.99, p = .003 respectively) and worse LFS (HR 1.62, p = .018; and 1.64, p = .011 respectively) while FLT3-ITD, MK, or other CG abnormalities had no significant effect. Importantly, CK negatively affected OS (HR 1.91, p = .002). In the first complete remission transplant setting, CK was found as the only cytogenetic risk factor for worse outcomes in NPM1-mutated AML. Nevertheless, even for this subgroup, a significant proportion of patients can achieve long-term posttransplant survival.
PICO Summary
Population
Adults with NPM1-mutated de novo AML with known cytogenetic and FLT3-ITD status, reported to the EBMT registry (n=3275)
Intervention
Analysis of the impact of high-risk cytogenetics (CG) on allogeneic hematopoietic cell transplantation in the first complete remission.
Comparison
None
Outcome
Overall, 2377 (73%) patients had FLT3-ITD. On univariate analysis, only FLT3-ITD, minimal/measurable residual disease (MRD) positivity and CK, but not abnormal CG, affected posttransplant outcomes. On multivariable analysis, CK was associated with lower overall survival (OS) (hazard ratio [HR] 1.72). In the subgroup of 493 patients with aberrant CG, the 2-year leukemia-free survival (LFS) and OS were around 61% and 68%, respectively. On multivariable analysis for this subgroup, CK and MRD positivity were associated with increased risk of relapse (HR 1.7, p = .025; and 1.99) and worse LFS (HR 1.62, p = .018; and 1.64 respectively) while FLT3-ITD, MK, or other CG abnormalities had no significant effect. Importantly, CK negatively affected OS (HR 1.91). In the first complete remission transplant setting, CK was found as the only cytogenetic risk factor for worse outcomes in NPM1-mutated AML.
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Finding a balance in reduced toxicity hematopoietic stem cell transplantation for thalassemia: role of infused CD3+ cell count and immunosuppression
Meissner, B., Lang, P., Bader, P., Hoenig, M., Müller, I., Meisel, R., Greil, J., Sauer, M. G., Metzler, M., Corbacioglu, S., et al
Bone marrow transplantation. 2024
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Editor's Choice
Abstract
We performed a retrospective analysis on 124 patients with transfusion-dependent thalassemia who were registered in the German pediatric registry for stem cell transplantation. All patients underwent first allogeneic hematopoietic stem cell transplantation (HSCT) between 2011 and 2020 and belonged mainly to Pesaro risk class 1-2. Four-year overall (OS) and thalassemia-free survival (TFS) were 94.5% ± 2.9% and 88.0% ± 3.4% after treosulfan-fludarabine-thiotepa- and 96.9% ± 3.1% (P = 0.763) and 96.9% ± 3.1% (P = 0.155) after busulfan-fludarabine-based conditioning. Mixed chimerism below 75% occurred predominantly in treosulfan-based regimens (27.5% versus 6.2%). OS and TFS did not differ significantly between matched sibling, other matched family and matched unrelated donor (UD) HSCTs (OS: 100.0%, 100.0%, 96.3% ± 3.6%; TFS: 96.5% ± 2.4%, 90.0% ± 9.5%, 88.9% ± 6.0%). However, mismatched UD-HSCTs performed less favorable (OS: 84.7% ± 7.3% (P = 0.029); TFS: 79.9% ± 7.4% (P = 0.082)). We generated a scoring system reflecting the risk to develop mixed chimerism in our cohort. The main risk-reducing factors were a high CD3+ cell count (≥6 × 10(7)/kg) in the graft, busulfan-conditioning, pre-conditioning therapy and low-targeted ciclosporin A trough levels. Acute GvHD grade III-IV in treosulfan-based concepts predominantly occurred in patients with UD and reduced GvHD prophylaxis but not in the context of high CD3+ cell doses. Taken together, this information might be used to develop more risk-adapted HSCT regimens for thalassemia patients.
PICO Summary
Population
Children and young adults with transfusion-dependent thalassemia who underwent first allogeneic transplant between 2011 and 2020 and were registered in the German pediatric registry for stem cell transplantation. (n=124)
Intervention
Treosulfan-fludarabine-thiotepa based conditioning (n=92)
Comparison
Busulfan-fludarabine-based conditioning (n=32)
Outcome
Four-year overall (OS) and thalassemia-free survival (TFS) were 94.5% ± 2.9% and 88.0% ± 3.4% after treosulfan-fludarabine-thiotepa- and 96.9% ± 3.1% and 96.9% ± 3.1% after busulfan-fludarabine-based conditioning. Mixed chimerism below 75% occurred predominantly in treosulfan-based regimens (27.5% versus 6.2%). OS and TFS did not differ significantly between matched sibling, other matched family and matched unrelated donor (UD) HSCTs (OS: 100.0%, 100.0%, 96.3% ± 3.6%; TFS: 96.5% ± 2.4%, 90.0% ± 9.5%, 88.9% ± 6.0%). However, mismatched UD-HSCTs performed less favorable (OS: 84.7% ± 7.3%; TFS: 79.9% ± 7.4%). We generated a scoring system reflecting the risk to develop mixed chimerism in our cohort. The main risk-reducing factors were a high CD3+ cell count (≥6 × 10(7)/kg) in the graft, busulfan-conditioning, pre-conditioning therapy and low-targeted ciclosporin A trough levels. Acute GvHD grade III-IV in treosulfan-based concepts predominantly occurred in patients with UD and reduced GvHD prophylaxis but not in the context of high CD3+ cell doses.
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Survival advantage of treosulfan plus fludarabine (FT14) compared to busulfan plus fludarabine (FB4) in active acute myeloid leukemia post allogeneic transplantation: an analysis from the European Society for Blood and Marrow Transplantation (EBMT) Acute Leukemia Working Party (ALWP)
Gavriilaki, E., Sakellari, I., Labopin, M., Bornhäuser, M., Hamladji, R. M., Casper, J., Edinger, M., Zák, P., Yakoub-Agha, I., Ciceri, F., et al
Bone marrow transplantation. 2023
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Editor's Choice
Abstract
We compared FT14 (fludarabine 150-160 mg/m(2), treosulfan 42 g/m(2)) versus FB4 (fludarabine 150-160 mg/m(2), busulfan 12.8 mg/kg) in acute myeloid leukemia (AML) transplanted at primary refractory/relapsed disease. We retrospectively studied: (a) adults diagnosed with AML, (b) recipients of first allogeneic hematopoietic stem cell transplantation (HSCT) from unrelated/sibling donor (2010-2020), (c) HSCT with primary refractory/relapsed disease, (d) conditioning regimen with FT14 or FB4. We studied 346 patients, 113 transplanted with FT14, and 233 with FΒ4. FT14 patients were significantly older, more frequently had an unrelated donor and had received a lower dose of fludarabine. Cumulative incidence (CI) of acute graft-versus-host disease (GVHD) grade III-IV and extensive chronic GVHD was similar. With a median follow-up of 28.7 months, 2-year CI of relapse was 43.4% in FT14 versus 53.2% in FB4, while non-relapse mortality (NRM) was respectively 20.8% versus 22.6%. This led to 2-year leukemia-free survival (LFS) of 35.8% for FT14 versus 24.2% in FB4, and overall survival (OS) of 44.4% versus 34%. Adverse cytogenetics and conditioning regimen independently predicted CI of relapse. Furthermore, conditioning regimen was the only independent predictor of LFS, OS, and GVHD-free/relapse-free survival. Therefore, our real-world multicenter study suggests that FT14 is associated with better outcomes in primary refractory/relapsed AML.
PICO Summary
Population
Adults identified from the EBMT registry, meeting the following criteria: diagnosed with AML, recipients of first allogeneic hematopoietic stem cell transplantation (HSCT) from unrelated/sibling donor (2010-2020), and with primary refractory/relapsed disease, (n=346)
Intervention
Fludarabine 150-160 mg/m(2), treosulfan 42 g/m(2) conditioning (FT14, n=113)
Comparison
Fludarabine 150-160 mg/m(2), busulfan 12.8 mg/kg) conditioning (FB4, n=233)
Outcome
FT14 patients were significantly older, more frequently had an unrelated donor and had received a lower dose of fludarabine. Cumulative incidence (CI) of acute graft-versus-host disease (GVHD) grade III-IV and extensive chronic GVHD was similar. With a median follow-up of 28.7 months, 2-year CI of relapse was 43.4% in FT14 versus 53.2% in FB4, while non-relapse mortality (NRM) was respectively 20.8% versus 22.6%. This led to 2-year leukemia-free survival (LFS) of 35.8% for FT14 versus 24.2% in FB4, and overall survival (OS) of 44.4% versus 34%. Adverse cytogenetics and conditioning regimen independently predicted CI of relapse. Furthermore, conditioning regimen was the only independent predictor of LFS, OS, and GVHD-free/relapse-free survival.
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7.
Sequential vs myeloablative vs reduced intensity conditioning for patients with myelodysplastic syndromes with an excess of blasts at time of allogeneic haematopoietic cell transplantation: a retrospective study by the chronic malignancies working party of the EBMT
Potter, V., Gras, L., Koster, L., Kroger, N., Sockel, K., Ganser, A., Finke, J., Labussiere-Wallet, H., Peffault de Latour, R., Koc, Y., et al
Bone marrow transplantation. 2023
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Editor's Choice
Abstract
The optimal conditioning for patients with higher risk MDS receiving potentially curative allogeneic haematopoietic stem cell transplant(allo-HCT) remains to be defined. This is particularly the case for patients with excess of blasts at time of allo-HCT. Sequential (Seq) conditioning, whereby chemotherapy is followed rapidly by transplant conditioning, offers an opportunity to decrease disease burden, potentially improving outcomes allo-HCT outcomes. Herein we present the only analysis comparing Seq to myeloablative (MAC) and reduced intensity conditioning (RIC) specifically focussed on MDS patients with excess of blasts at allo-HCT. 303 patients were identified in the EBMT registry, receiving RIC (n = 158), Seq (n = 105), and MAC (n = 40). Median follow-up was 67.2 months and median age at allo-HCT was 59.5 years (IQR 53.5-65.6). For the entire cohort, 3 y overall survival (OS) was 50% (95% CI 45-56%) and relapse free survival (RFS) 45% (95% CI 40-51%). No significant differences in OS (log-rank p = 0.13) and RFS (log-rank p = 0.18) were observed between conditioning protocols. On multivariable analysis, lower performance status, worse IPSS-R cytogenetics, sibling donor (compared to 8/8 MUD) and ≥20% blasts at allo-HCT were associated with worse outcomes. In conclusion, the Seq protocol did little to influence the outcome in this high-risk group of patients, with outcomes mostly determined by baseline disease risk and patient characteristics such as performance status.
PICO Summary
Population
Patients with myelodysplastic syndrome (MDS) with excess of blasts at allo-HCT, identified from the EBMT registry (n=303)
Intervention
Sequential conditioning, where chemotherapy is followed rapidly by transplant (Seq, n=105)
Comparison
Reduced intensity conditioning (RIC, n=158), or myeloablative conditioning (MAC, n=40).
Outcome
Median follow-up was 67.2 months and median age at allo-HCT was 59.5 years (IQR 53.5-65.6). For the entire cohort, 3 y overall survival (OS) was 50% (95% CI 45-56%) and relapse free survival (RFS) 45% (95% CI 40-51%). No significant differences in OS and RFS were observed between conditioning protocols. On multivariable analysis, lower performance status, worse IPSS-R cytogenetics, sibling donor (compared to 8/8 MUD) and ≥20% blasts at allo-HCT were associated with worse outcomes.
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8.
Impact of Second Primary Malignancy Post-Autologous Transplantation on Outcomes of Multiple Myeloma: A CIBMTR Analysis
Ragon, B. K., Shah, M. V., D'Souza, A., Estrada-Merly, N., Gowda, L., George, G., DeLima, M., Hashmi, S., Kharfan-Dabaja, M. A., Majhail, N. S., et al
Blood advances. 2023
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Editor's Choice
Abstract
The overall survival (OS) has improved significantly in multiple myeloma (MM) over the last decade with use of proteasome inhibitor and immunomodulatory drug-based combinations, followed by high-dose melphalan and autologous hematopoietic stem cell transplantation (auto-HSCT) and subsequent maintenance therapies in eligible newly diagnosed patients. However, clinical trials employing auto-HSCT followed by lenalidomide maintenance have shown an increased risk of second primary malignancies (SPM), including second hematological malignancies (SHM). We evaluated the impact of SPM and SHM on progression-free survival (PFS) and OS in MM patients following auto-HSCT using CIBMTR registry data. Adult MM patients who underwent first auto-HSCT in the United States with melphalan conditioning regimen from 2011 to 2018 and received maintenance therapy were included (n=3,948). At a median follow up of 37 months, 175 (4%) patients developed SPM, including 112 (64%) solid, 36 (20%) myeloid, 24 (14%) SHM, not otherwise specified, and 3 (2%) lymphoid malignancies. Multivariate analysis demonstrated that SPM and SHM were associated with an inferior PFS (HR 2.62, P<.001 and HR 5.01, P<.001, respectively) and OS (HR 3.85, P<.001 and HR 8.13, P<.001, respectively). In patients who developed SPM and SHM, MM remained the most frequent primary cause of death (42% versus 30% and 53% versus 18%, respectively). We conclude the development of SPM and SHM leads to a poor survival in MM patients and is an important survivorship challenge. Given the median survival for MM continues to improve, continued vigilance is needed to assess the risks of SPM and SHM with maintenance therapy post-auto-HSCT.
PICO Summary
Population
Drawn from the CIBMTR registry, adults with multiple myeloma (MM) who underwent first auto-HSCT with melphalan conditioning regimen and received maintenance therapy (n=3,948)
Intervention
Identification of second primary malignancies (SPM) or second haematological malignancies (SHM) following HSCT.
Comparison
None
Outcome
At a median follow up of 37 months, 175 (4%) patients developed SPM, including 112 (64%) solid, 36 (20%) myeloid, 24 (14%) SHM, not otherwise specified, and 3 (2%) lymphoid malignancies. Multivariate analysis demonstrated that SPM and SHM were associated with an inferior PFS (HR 2.62 and HR 5.01 respectively) and OS (HR 3.85, and HR 8.13, respectively). In patients who developed SPM and SHM, MM remained the most frequent primary cause of death (42% versus 30% and 53% versus 18%, respectively).
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9.
Allogeneic hematopoietic stem cell transplantation in patients aged 60-79 years in Germany (1998-2018): a registry study
Weller, J. F., Lengerke, C., Finke, J., Schetelig, J., Platzbecker, U., Einsele, H., Schroeder, T., Faul, C., Stelljes, M., Dreger, P., et al
Haematologica. 2023
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Editor's Choice
Abstract
Incidences of diseases treated with transplantation frequently peak at higher age. The contribution of age to total risk of transplantation has not been estimated amidst an aging society. We compare outcomes of 1,547 patients aged 70-79 and 9,422 patients aged 60-69 transplanted 1998-2018 for myeloid, lymphoid and further neoplasia in Germany. To quantify the contribution of population mortality to survival, we derive excess mortality based on a sex-, year- and age-matched German population in a multistate model that incorporates relapse and graft-versus-host-disease (GvHD). Overall, relapse-free (RFS) and GvHD-free-relapse-free survival (GRFS) is inferior in patients 70-79, compared to patients 60-69, with 36% [95%CI 34-39%] versus 43% [41-44%], 32% [30-35%] versus 36% [35-37%] and 23% [21-26%] versus 27% [26-28%] three years post-transplant (p<0.001). Cumulative incidences of relapse at three years are 27% [25-30%] (patients 70-79) versus 29% [29-30%] (60-69, p=0.71), yet the difference in non-relapse mortality (NRM, 40% [38-43%] versus 35% [34-36%] in 70-79 versus 60-69 aged patients, p<0.001) translates into survival differences. Median OS of patients surviving >1 year relapse-free is 6.7 (median, 95%CI 4.5-9.4, 70-79) versus 9 (8.4-10.1, 60-69) years since landmark. Three years after RFS of 1 year, excess NRM is 14% [95%CI 12-18%] in 70-79 versus 12% [11-13%] in 60-69, while population NRM is 7% [6-7%] versus 3% [3-3%]. Mortality for reasons other than relapse, GvHD or age is as high as 27% [24-29%] and 22% [22-23%] 4 years after transplantation. In conclusion, survival amongst older patients is adequate after allogeneic stem cell transplantation.
PICO Summary
Population
Adults aged 60 years and over, receiving first allogeneic transplant for any malignant disease, identified from the German registry for stem cell transplantation (n=10,969)
Intervention
Transplant aged 70-79 years (n=1,547)
Comparison
Transplant aged 60-69 years (n=9,422)
Outcome
Overall, relapse-free (RFS) and GvHD-free-relapse-free survival (GRFS) is inferior in patients 70-79, compared to patients 60-69, with 36% [95%CI 34-39%] versus 43% [41-44%], 32% [30-35%] versus 36% [35-37%] and 23% [21-26%] versus 27% [26-28%] three years post-transplant. Cumulative incidences of relapse at three years are 27% [25-30%] (patients 70-79) versus 29% [29-30%] (60-69), yet the difference in non-relapse mortality (NRM, 40% [38-43%] versus 35% [34-36%] in 70-79 versus 60-69 aged patients translates into survival differences. Median OS of patients surviving >1 year relapse-free is 6.7 (median, 95%CI 4.5-9.4, 70-79) versus 9 (8.4-10.1, 60-69) years since landmark. Three years after RFS of 1 year, excess NRM is 14% [95%CI 12-18%] in 70-79 versus 12% [11-13%] in 60-69, while population NRM is 7% [6-7%] versus 3% [3-3%]. Mortality for reasons other than relapse, GvHD or age is as high as 27% [24-29%] and 22% [22-23%] 4 years after transplantation.
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Real-world data showing trends and outcomes by race and ethnicity in allogeneic hematopoietic cell transplantation: a report from the Center for International Blood and Marrow Transplant Research
Auletta, Jj Md, Kou, J. Ms, Chen, M. Ms, Bolon, Y. T. PhD, Broglie L Md, M. S., Bupp, C. Mph, Christianson, D. Ba, Cusatis, R. N. PhD, Devine, Sm Md, Eapen M Mbbs, M. S., et al
Transplantation and cellular therapy. 2023
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Editor's Choice
Abstract
BACKGROUND Use of human leukocyte antigen (HLA)-mismatched donors could enable more patients with ethnically diverse backgrounds to receive allogeneic hematopoietic cell transplantation (HCT) in the United States. However, real-world trends and outcomes following mismatched donor HCT for diverse patients remain largely undefined. OBJECTIVE To determine whether mismatched donor platforms have increased access to allogeneic HCT for ethnically diverse patients, particularly through the application of novel graft-versus-host disease (GvHD) prophylaxis regimens, and if outcomes for diverse patients were comparable to those of non-Hispanic White patients. DESIGN Observational cross-sectional study using real-world data from the Center for International Blood and Marrow Transplant Research (CIBMTR) registry. All patients receiving their first allogeneic HCT in the U.S. from 2009-2020 with focus on transplants performed in 2020 were included. Data from patients receiving allogeneic HCT using bone marrow, peripheral blood or cord blood from HLA-matched or mismatched related and unrelated donors was analyzed. Specifically, relative proportions of allogeneic HCT were generated as percent of total for donor type and for patient age, disease indication, GvHD prophylaxis, and race and ethnicity. Causes of death were summarized using frequencies, and the Kaplan-Meier estimator was used for estimating overall survival. RESULTS Compared to matched related donor and matched unrelated donor HCT, more ethnically diverse patients received mismatched unrelated donor, haploidentical donor, and cord blood HCT. Matched unrelated donor remains the most common donor type, but use of haploidentical donors has increased significantly over the last 5 years. Paralleling the increase in haploidentical HCT is the increased use of post-transplant cyclophosphamide (PTCy) as GvHD prophylaxis. Relative to older transplant eras, the most contemporary transplant era associates with the highest survival rates following allogeneic HCT irrespective of patient race and ethnicity. However, disease relapse remains the primary cause of death for both adult and pediatric allogeneic HCT recipients by donor type and across all patient race and ethnicity groups. CONCLUSIONS Ethnically diverse patients are undergoing allogeneic HCTs at higher rates largely through the use of alternative donor platforms incorporating PTCy. Maintaining access to potential life-saving allogeneic HCT using alternative donors and novel GvHD prophylaxis strategies and improving HCT outcomes, particularly disease relapse, are urgent clinical needs.
PICO Summary
Population
All patients receiving their first allogeneic HCT in the U.S. from 2009-2020, identified from the CIBMTR registry (n=93,790)
Intervention
Relative proportions of recipients according to donor type and for patient age, disease indication, GvHD prophylaxis, and race and ethnicity for the 2020 cohort (n=8,326)
Comparison
Relative proportions of recipients according to donor type and for patient age, disease indication, GvHD prophylaxis, and race and ethnicity for the 2009-2019 cohort (n=85,464)
Outcome
Compared to matched related donor and matched unrelated donor HCT, more ethnically diverse patients received mismatched unrelated donor, haploidentical donor, and cord blood HCT. Matched unrelated donor remains the most common donor type, but use of haploidentical donors has increased significantly over the last 5 years. Paralleling the increase in haploidentical HCT is the increased use of post-transplant cyclophosphamide (PTCy) as GvHD prophylaxis. Relative to older transplant eras, the most contemporary transplant era associates with the highest survival rates following allogeneic HCT irrespective of patient race and ethnicity. However, disease relapse remains the primary cause of death for both adult and pediatric allogeneic HCT recipients by donor type and across all patient race and ethnicity groups.